The estrogen receptor-related receptors (ERRs) are a group of orphan nuclear receptors that were originally identified due to sequence similarity to estrogen receptors (ERs). In mammals, ERR expression can be upregulated by estrogen exposure. Mammalian ERRs can also share target genes, ligands and cofactors with ERs. Physiological functions for ERRs have been proposed, including roles in bone development, placentation and energetic metabolism; however, characterization of ERR function is incomplete, and the potential for disruption of ERR signaling by environmental contaminants is largely unknown. The main objective of this research is to characterize the function of ERRs in the zebrafish as a model to improve understanding of ERR function in humans. The specific aims of this project are to (1) mechanistically characterize zebrafish ERRs and the effects of ligands on ERR activity, (2) determine spatial patterns of ERR expression in adult zebrafish and measure the effects of estrogen exposure on ERR expression, and (3) identify developmental patterns of ERR expression and phenotypic changes associated with "knocking down" ERR expression during zebrafish embryonic development. [unreadable] [unreadable]